Mechanisms of Cell Death in Spinal Muscular Atrophy

NCT01754441 | Completed

• 1 other identifier: 82008
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

Spinal muscular atrophy is a genetically based disease that affects motor neurons in the spinal cord and leads to muscle wasting and weakness. The gene found to be responsible for the underlying disease is called the SMN or survival motor neuron gene. Individuals with SMA are either missing a copy of the gene or have a mutation in the gene. Although the gene has been identified, how it actually causes the motor neurons to die and leads to muscle wasting and weakness is not completely understood. The investigators have found that skin cells from children with SMA tend to be more susceptible to cell death when exposed to cell death inducing agents. In this protocol, The investigators wish to study the mechanisms by which these cells die when exposed to these agents and how this may be related to the gene defect and the disease.

Conditions

Spinal Muscular Atrophy

Keywords

Spinal Muscular Atrophy; SMA; Motor Neuron Abnormalities

Outcome Measures

Primary Outcomes (1)

• SMN localization in SMA fibroblasts

  Established fibroblast lines from SMA patients will be immunolabeled with antibodies directed against SMN and examined for changes in the nuclear localization of SMN in gems.

  up to 2 years

Secondary Outcomes (6)

• SMN isoform mRNA levels

  up to 2 years

• Protein levels of putative SMA phenotypic modifiers

  up to 2 years

• cell viability in response to DNA damaging agents

  up to 2 years

• SMN protein levels

  up to 2 years

• cell viability in response to cell death-inducing agents

  up to 2 years

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

This study will enroll Children with Spinal Muscular Atrophy (SMA)

You may qualify if:

• Diagnosis of SMA confirmed by neurologist

You may not qualify if:

• Not seen as a patient at a participating Nemours facility

Sponsors & Collaborators

• Nemours Children's Clinic: lead

Study Sites (2)

Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Nemours Children's Specialty Care, Jacksonville

Jacksonville, Florida, 32207, United States

Location

Related Publications (2)

• Stabley DL, Harris AW, Holbrook J, Chubbs NJ, Lozo KW, Crawford TO, Swoboda KJ, Funanage VL, Wang W, Mackenzie W, Scavina M, Sol-Church K, Butchbach ME. SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR. Mol Genet Genomic Med. 2015 Jul;3(4):248-57. doi: 10.1002/mgg3.141. Epub 2015 Mar 21.

  PMID: 26247043 RESULT

• Stabley DL, Holbrook J, Harris AW, Swoboda KJ, Crawford TO, Sol-Church K, Butchbach MER. Establishing a reference dataset for the authentication of spinal muscular atrophy cell lines using STR profiling and digital PCR. Neuromuscul Disord. 2017 May;27(5):439-446. doi: 10.1016/j.nmd.2017.02.002. Epub 2017 Feb 6.

  PMID: 28284873 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Skin biopsy specimens

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Study Officials

• Matthew ER Butchbach, Ph.D.

  Nemours Biomedical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Scientist

Study Record Dates

• First Submitted: December 13, 2012
• First Posted: December 21, 2012
• Study Start: May 1, 2008
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: February 21, 2020

Record last verified: 2020-02

Locations

US (2)